Liposomes are self-assembled vesicles having a spherical bilayer structure surrounding an aqueous core domain. Due to their intrinsic biocompatibility and ease of preparation, several liposomal drugs have been approved (Torchilin, 2005, Nat. Rev. Drug Discov. 4:145-160). In addition, modified liposomes on the nanoscale (20-200 nm) have been shown to have excellent pharmacokinetics profiles for the delivery of nucleic acids, proteins, and chemotherapeutic agents such as doxorubicin (Papahadjopoulos et al., 1991, Proc. Natl. Acad. Sci. 88:11460-11464; Eliaz et al., 2001, Cancer Res. 61:2592-2601). However, major drawbacks of liposome-based drug carriers include their instability and the lack of tunable triggers for drug release. As such, there have been several attempts at enhancing the properties of liposomes (Torchilin, 2005; Ringsdorf et al., 1988, Angew. Chem. Int. Ed. 27:113-158). Incorporation of polymerizable lipid amphiphiles leads to crosslinked liposomes with higher stability (O'Brien et al., 1998, Acc. Chem. Res. 31:861-868). Unfortunately, every lipid system would require a specific polymerizable amphiphile, making this approach synthetically cumbersome. In addition, the crosslinks are often too stable to allow for controllable release of the payload. To provide a combination of stability and modification generality, hydrophilic polymers such as poly(ethylene glycol) (PEG) (Papahadjopoulos et al., 1991) and poly(N-isopropylacrylamide) (Ringsdorf et al., 1988) have been added to liposomes. However, these modifiers can easily dissociate from the liposome surface, returning them to the unstable state (Adlakha-Hutcheon et al., 1999, Biotechnol. 17:775-779; Silvius et al., 1993, Biochem. 32:3153-3161; Holland et al., 1996, Biochem. 35:2618-2624).
As such, what are needed are liposomal constructs that will accommodate a wide variety of payloads (e.g., nucleic acids, peptides, small molecules, drugs, etc.), maintain stability, and deliver the payload to the intended location.